More than 100 million Americans suffer from chronic pain. Furthermore, problems with use of illicit drugs include pain-reliever misuse, abuse, and addiction. Because of this, it is increasingly difficult for patients with legitimate medical needs for opioid-containing drugs, like Vicodin, to obtain prescriptions. The U.S. Substance Abuse and Mental Health Services Administration estimated 20.1 million Americans were illicit-drug users and an estimated 4.7 million of those persons used pain relievers non-medically in 2008. Thus, an effective treatment for chronic pain that has less addictive potential and abuse liability is a major unmet need in medicine today.
Transient receptor potential cation channel, subfamily A, member 1, (“TRPA1”; wild-type, SEQ ID NO:1; variants, SEQ ID NOS:2-7) is a a non-selective cation channel present in mammalian cells. TRPA1-receptor/channels play a highly specific function in sensory nerves that transmit the sensations of pain and hyperalgesia in response to inflammation as well as nerve injury, particularly in chronic conditions. Recent progress in understanding the function and identification of endogenous ligands for TRPA1 channels suggests that TRPA1 is relevant to detecting nociceptive signals.